A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.

GTEx Eligibility Requirements. A set of eligibility requirements were developed to align with the scientific needs of the project and to reduce the risk of collecting tissue that was diseased, autolyzed, or otherwise unsuitable for molecular analysis. The eligibility criteria were developed within a framework that considered the limited data immediately available in the timeframe surrounding a potential donor's death and the feasibility of the Biospecimen Source Sites to obtain the tissues and associated data in a timely manner.

The GTEx Biospecimen Collection Infrastructure. The GTEx Biospecimen Source Sites were responsible for donor recruitment, tissue procurement and processing, and data collection. Brain and hair samples were sent to the Miami Brian Bank for quality control purposes, coronal sectioning of brain tissue, and storage of brain tissue. The Comprehensive Biospecimen Resource handled biospecimen receipt, processing, distribution and storage, histology and imaging, and kit development and production. The Comprehensive Data Resource is a data repository that served as an honest broker to keep limited data set information confidential and distribute de-identified data. The Pathology Resource Center performed case review through tissue identification and quality assessments. The Laboratory, Data Analysis, and Coordinating Center conducted molecular and data analysis as well as served as a project management and data-coordinating center. Clinical, demographic, handling, genetic and molecular data from GTEx biospecimens can be accessed through the National Center for Biotechnology Information's database of Genotypes and Phenotypes. Color images available online at www.liebertpub.com/bio

GTEx Pathology Review. Certain tissues were not considered acceptable for GTEx analysis purposes. (a, b) Autolysis. (a) Well-preserved pancreas with distinguishable exocrine and endocrine elements (RNA integrity number [RIN] 6.3). (b) Severely autolyzed pancreas (RIN 2.4). (c, d) Heterogeneous tissue sampling. (c) Well-preserved gastric mucosa with a RIN of 7.3. The higher RIN reflects multiple cell types: the abundant well-fixed gastric glands in the mucosal layer combined with muscularis mucosa. (d) Poorly preserved colon mucosa with a RIN of 7.3. Although the mucosa was also the intended target in this biospecimen, it was badly autolyzed and the RIN reflects the residual colon muscularis propria. (e, f) Acceptable diseased tissues. (e) Normal thyroid. (f) Thyroid with Hashimoto's germinal center formation was identified but was still considered to be eligible for the GTEx study. Color images available online at www.liebertpub.com/bio

The number and type of GTEx tissues collected. 41 different PAXgene preserved tissues types were collected for the GTEx project. Six tissues were female specific and two tissues were male specific. Only five tissues were mandatory for each case collected, which partially explains the significant differences among the number of tissues collected per tissue type.

GTEx RIN values. Here we show the average RNA integrity number (RIN) values by tissue type for 190 cases. Twenty-four tissue types had average RNA integrity values greater than 6 during the pilot study.

The effect of ischemic time on RIN values. RIN values greatly decreased when the postmortem interval (PMI) was ≥8 hours. PMI is based on interval between the time of death or the cessation of blood flow and the time that the last tissue is placed in preservative.